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Chunk #33 — Online Methods — Enrichment of disease-associated variants among fetal brain mQTLs

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Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci.
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A similar simulation procedure to that used to test the overlap of mQTLs and eQTLs was used to test for a larger overlap between fetal brain mQTL SNPs and those identified in GWAS of complex disorders including: schizophrenia12, Alzheimer’s disease32, body mass index (BMI)33, and type 2 diabetes34. The clumping procedure as described for the eQTL enrichment analysis was repeated separately for each phenotype to ensure that the best mQTL SNP present in those analysed in the GWAS was retained. Up to 1 million simulations were performed to generate the expected overlap between the set of mQTL SNPs and variants associated with each disorder at four GWAS significance thresholds (P < 5×10−5, 5×10−6, 5×10−7, 5×10−8) and derive fold change statistics and empirical P values.